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The COMP Division is excited to announce the OpenEye Award winners for the Indianapolis ACS meeting (fall 2013). Please visit the COMP award winners and the other excellent COMP posters at the COMP Poster Session on Tuesday, September 10, 2013 from 6pm to 8pm at a location to be determined.

A detailed knowledge of the role water plays in biomolecular interactions is crucial to understand protein folding or biomolecular recognition. Methodologies to compute the thermodynamic properties of discrete sets of water molecules are increasingly used to support drug-discovery efforts. However it is not always possible to rationalise biomolecular hydration thermodynamics with a simple discrete distributions of water molecules. This poster will describe ongoing efforts to develop the grid cell theory method to resolve and visualize the thermodynamic properties of water over arbitrarily complex regions of space in the vicinity of a biomolecule. The robustness and versatility of the methodology will be demonstrated on diverse systems, ranging from small molecules to proteins. I will discuss ongoing efforts to: enhance convergence of solvent distributions; characterise biomolecules-induced perturbations in water structure; estimate ligand-induced changes in binding site hydration thermodynamics.

Enabling Chemical Discovery through the Lens of a Computational Microscope

With exascale computing power on the horizon, computational studies have the opportunity to make unprecedented contributions to drug discovery efforts. Steady increases in computational power, coupled with improvements in the underlying algorithms and available structural experimental data, are enabling new paradigms for discovery, wherein computationally predicted ensembles from large-scale biophysical simulations are being used in rational drug design efforts. Such investigations help drive discovery efforts and experimental work on these systems in collaboration with leading experimentalists. Our work in this area has provided key insights into the systematic incorporation of structural information resulting from state-of-the-art biophysical simulations into protocols for inhibitor and drug discovery. In addition to the scientific advances, my lab has also developed freely-distributed, open source tools and technologies that assist the broader community in ensemble-structural selection and analyses to support simulation-based discovery efforts.

In this poster, I will present the overall strategy to use structures generated from molecular dynamics simulations in combination with virtual screening, which I pioneered as a postdoctoral scholar. As an independent PI, the emphasis of my lab has been on the exploration of these “high risk” methods in discovery. We have made substantial progress in these areas, including new discoveries for influenza, trypanosomiasis, agents against emerging pathogens, and cancer. Work to improve these methods, including the incorporation of more rigorous statistical models, is ongoing. I will also present my work in open source tool development for the community. Here, we have created a VMD plugin that computes ensemble-averaged electrostatic potential maps for arbitrary biomolecules using DelPhi. Very recently, we also developed a tool that assists in the analysis of computational solvent mapping across ensembles of structures.

Through numerical simulation we demonstrate the existence of the Fano interference effect in the electron energy-loss spectroscopy (EELS) and cathodoluminescence (CL) of symmetry-broken nanorod dimers that are heterogeneous in both material composition and length. The differing selection rules of the electron probe in comparison to the photon of a plane wave allow for the simultaneous excitation of both optically bright and dark plasmons of each monomer unit. Yet, interferences are manifested in the dimer's scattered near- and far-fields due to the rapid π-phase offset in the polarizations between super-radiant and sub-radiant hybridized plasmon modes of the dimer as a function of the energy loss suffered by the impinging electron. Depending upon the location of the electron beam, we predict the conditions under which Fano interferences will be present in both optical and electron spectroscopies (EELS and CL) as well as a new class of Fano interferences that are uniquely electron-driven and are absent in the optical response.

I will present several approaches increasing both the efficiency and accuracy of ultrafast spectra calculations. First, we prove that the number of trajectories needed for evaluating such spectra with the semiclassical Dephasing Representation (DR) is independent of dimensionality [1]. This general result justifies the feasibility of quantum calculations of time-resolved electronic spectra of large systems. The method is further accelerated by developing the Cellular Dephasing Representation in which the number of trajectories is drastically reduced—spectra based on a single semiclassical trajectory are in a remarkable agreement with the fully converged DR requiring 104 trajectories [2]. Second, the accuracy is improved by combining the DR with accurate on-the-fly ab initio electronic structure calculations, including nonadiabatic and spin-orbit couplings [3], and by removing the inherent semiclassical approximation [4]. By starting from an exact Gaussian basis method, the DR is derived together with ten new methods for computing time-resolved spectra with intermediate accuracy and efficiency. These methods include the Gaussian DR, an exact generalization of the DR, in which trajectories are replaced by communicating frozen Gaussian basis functions evolving classically with an average Hamiltonian. Surprisingly, in chaotic systems the Gaussian DR can outperform the presumably more accurate Gaussian basis method. The newly developed methods are tested on several systems of increasing complexity. Our time-resolved stimulated emission spectrum of the 54-dimensional azulene is at present the largest ab initio semiclassical dynamics calculation of a coherent spectrum. Our Multiple Surface DR provides theoretical justification of the violation of Kasha's rule of excited-state photochemistry in azulene.

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